Towards salivary C-reactive protein as a viable biomarker of systemic inflammation.

C-reactive protein (CRP) is a commonly used marker of systemic inflammation, routinely measured in serum blood samples. However salivary samples offer a non-invasive and easily accessible alternative which would improve point of care (POC) testing for inflammation. Two major challenges restrict the use of saliva: the influence of the oral environment on CRP and its local production; and collecting a standardised sample given patient-dependent salivary flow rates. Here we review the reported studies of salivary CRP in humans as a potential marker of systemic inflammation and how the challenges can be overcome. Salivary CRP currently poorly reflects systemic inflammation as it does not consistently and strongly correlate with serum CRP. The mean and one standard deviation reported R2 values are 0.53 ± 0.23 from 14 studies. An improved understanding of the key challenges and implemented solutions are needed to optimise salivary CRP use. Firstly, control for the effects of local oral inflammation. Screening for oral trauma is one option, however this could drastically limit the number of patients suitable for salivary CRP testing and the number of professionals able to use the POC test. Secondly, the role of a dilution biomarker is considered controlling for salivary flow rate which dilutes serum CRP by ~104; a variable and likely-patient specific factor. The ideal dilution biomarker should have many of the pharmacokinetic, sensitivity and specificity characteristics of CRP. The potential for positive acute phase protein serum amyloid A (SAA) and negative acute phase protein albumin is considered and the characteristics of any correction function discussed. Currently, however, there are no available strategies to make salivary CRP a reliable quantitative measure of serum CRP and hence POC systemic inflammation testing.